Abstract: FR-PO663
Increased Odds of Nephrotic Syndrome and ESKD in Fin-Major Heterozygotes
Session Information
- Genetic Kidney Diseases: Cohort Studies - Genetic Associations and Diagnoses
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Banerji, Adrian Olaf, Boston Children's Hospital, Boston, Massachusetts, United States
- Palotie, Aarno, Helsingin yliopisto, Helsinki, Uusimaa, Finland
- Sampson, Matt G., Boston Children's Hospital, Boston, Massachusetts, United States
Group or Team Name
- FinnGen.
Background
NPHS1 loss of function (LOF) variants are known to cause congenital nephrotic syndrome (NS) with recessive inheritance. Fin-Major was the first described NPHS1 LOF variant. The clinical impact of Fin-Major in the heterozygous state is incompletely understood. We assessed the prevalence of nephrotic syndrome and end stage kidney disease (ESKD) for Fin-Major heterozygotes in the FinnGen study, in which 10% of the Finnish population (n=520,212) is enrolled.
Methods
The FinnGen database was used to identify individuals heterozygous for Fin-Major, and those without identified NPHS1 variants. Patients homozygous for Fin-Major or with at least one other NPHS1 variant were excluded, thereby excluding known compound heterozygotes. Individuals without identified NPHS1 variants were used as controls. Individuals with NS or ESKD (chronic dialysis or kidney transplant) were identified by ICD-10 code. As these are chronic conditions, only individuals with repeated codes for each condition were included for further analysis.
Results
Among all FinnGen participants, 8,944 individuals were heterozygous for Fin-Major, 859 had NS, and 3,536 had ESKD. Individuals heterozygous for Fin-Major had 2 times increased odds to have nephrotic syndrome and 1.5 times increased odds to have ESKD compared to those without Fin-Major (P<0.001). After exclusion of Fin-Major heterozygotes with congenital NS (n=8), Fin-Major heterozygous individuals had 1.4 times increased odds to have nephrotic syndrome and 1.3 times increased odds to have ESKD (p=0.1, p=0.01).
Conclusion
Individuals heterozygous for the Fin-Major variant have increased risk for nephrotic syndrome and ESKD. This persists even after exclusion of individuals with congenital nephrotic syndrome. Further work, including exome sequencing of NPHS1, is needed to identify if this risk is due to unrecognized compound heterozygosity or if NPHS1 haplo-insufficiency is a contributor to kidney disease risk.
Funding
- NIDDK Support